Type |
Article |
Date |
2016-05 |
Language |
English |
Author(s) |
Qin Wei1, Bazeille Nicolas2, Henry Etienne2, Zhang Bo1, Deprez Eric2, Xi Xu-Guang1, 2 |
Affiliation(s) |
1 : Northwest A&F Univ, Coll Life Sci, Yangling 712100, Shaanxi, Peoples R China. 2 : Univ Paris Saclay, ENS Cachan, IDA FR3242, LBPA,CNRS UMR8113, F-94235 Cachan, France. |
Source |
Scientific Reports (2045-2322) (Nature Publishing Group), 2016-05 , Vol. 6 , N. 26225 , P. 12p. |
DOI |
10.1038/srep26225 |
WOS© Times Cited |
13 |
Abstract |
Cadmium is a toxic metal that inactivates DNA-repair proteins via multiple mechanisms, including zinc substitution. In this study, we investigated the effect of Cd2+ on the Bloom protein (BLM), a DNA-repair helicase carrying a zinc-binding domain (ZBD) and playing a critical role to ensure genomic stability. One characteristics of BLM-deficient cells is the elevated rate of sister chromatid exchanges, a phenomenon that is also induced by Cd2+. Here, we show that Cd2+ strongly inhibits both ATPase and helicase activities of BLM. Cd2+ primarily prevents BLM-DNA interaction via its binding to sulfhydryl groups of solvent-exposed cysteine residues and, concomitantly, promotes the formation of large BLM multimers/aggregates. In contrast to previously described Cd2+ effects on other zinc-containing DNA-repair proteins, the ZBD appears to play a minor role in the Cd2+-mediated inhibition. While the Cd2+-dependent formation of inactive multimers and the defect of DNA-binding were fully reversible upon addition of EDTA, the inhibition of the DNA unwinding activity was not counteracted by EDTA, indicating another mechanism of inhibition by Cd2+ relative to the targeting of a catalytic residue. Altogether, our results provide new clues for understanding the mechanism behind the ZBD-independent inactivation of BLM by Cd2+ leading to accumulation of DNA double-strand breaks. |
Full Text |
File |
Pages |
Size |
Access |
Publisher's official version |
12 |
1 MB |
Open access |
Supplementary Information |
8 |
654 KB |
Open access |
|